Which step of the Citric Acid Cycle is considered the rate-limiting step?

The rate-limiting step of the Citric Acid Cycle, also known as the Krebs cycle, is typically the conversion of oxaloacetate to citrate. This reaction is catalyzed by the enzyme citrate synthase. It is considered the rate-limiting step because it is tightly regulated and highly exergonic, meaning it releases a significant amount of energy, thus driving the cycle forward.

In this context, the reaction involves the condensation of oxaloacetate with acetyl-CoA to form citrate. This step is crucial because it effectively commits the substrates to undergo further reactions in the cycle, and it determines the overall pace of the cycle. The availability of acetyl-CoA and the concentrations of oxaloacetate and citrate synthase influence the rate of this reaction, making it a key point of regulation within the cycle.

The other steps, while important, do not serve as the primary regulatory point. They may be influenced by product inhibition or feedback from downstream pathways, but they do not exhibit the same level of control over the cycle as the reaction catalyzed by citrate synthase does. Therefore, the conversion of oxaloacetate to citrate is recognized as the rate-limiting step in the Citric Acid Cycle.